Using biomaterials to promote pro-regenerative glial phenotypes after nervous system injuries

Trauma to either the central or peripheral nervous system (PNS) often leads to significant loss of function and disability in patients. This high rate of long-term disability is due to the overall limited regenerative potential of nervous tissue, even though the PNS has more regenerative potential than the central nervous system (CNS). The supporting glial cells in the periphery, Schwann cells, are part of the reason for the improved recovery observed in the PNS. In the CNS, the glial populations, astrocytes and oligodendrocytes (OLs), do not have as much potential to promote regeneration and are at times inhibitory to neuronal growth. In particular, the inhibitory roles astrocytes play following trauma has led to a historical focus on neurons and OLs instead of astrocytes. Recently, this focus has shifted as new, regenerative astrocyte phenotypes have been described. From these observations, glial cells clearly play critical roles in native recovery pathways in both the CNS and PNS. This makes the ability to manipulate both transplanted and native glial cell phenotypes a potentially successful strategy to improve nerve injury outcomes. This review focuses on factors that cause glial cells to adopt repair phenotypes and biomaterials that manipulate and/or harness these glial phenotypes.